A closer look at ultrasonic attenuation and heating in a tissue-mimicking material.

A well-characterized ultrasound tissue-mimicking material (TMM) can be important in determining the acoustic output and temperature rise from high intensity therapeutic ultrasound (HITU) devices and also in validating computer simulation models. A HITU TMM previously developed and characterized in our laboratory has been used in our acoustic and temperature measurements as well as modeled in our HITU simulation program. A discrepancy between thermal measurement and simulation, though, led us to further investigate the TMM properties. We found that the 2-parameter analytic fit commonly used to represent the attenuation of the TMM in the computer modeling was not adequate over the entire frequency range of interest, 1 MHz to 8 MHz in this study, indicating that we and others may have not been characterizing TMMs, and possibly tissue, optimally. By comparing measurements and simulations, we found that a 3-parameter analytic fit for attenuation gave a more accurate value for attenuation at 1 MHz and 2 MHz, and using that fit the temperature rise measurements in the TMM that agreed more closely with the simulation results.

In-Vitro Pulsatile Flow Measurement in Prosthetic Heart Valves: An Inter-Laboratory Comparison.

BACKGROUND AND AIM OF STUDY: One of the first steps in qualifying a new prosthetic valve for eventual clinical use is preclinical flow performance testing in vitro. Such testing is typically performed in an in-vitro test system that simulates the pumping mechanics of the left ventricle of the heart, generally referred to as a pulse duplicator or duplicator. Historically, test results in these systems have varied from duplicator to duplicator. This collaborative effort between heart valve manufacturers and the Food and Drug Administration (FDA) was designed to evaluate the variability of the pulse duplicator test technology for pulsatile flow performance measurement in an interlaboratory round robin. METHODS: The participants jointly developed and followed a limited test protocol based on accepted methods outlined in the International Standards Organization 5840: Cardiovascular Implants - Cardiac Valve Prostheses, and in the FDA Replacement Heart Valve Guidance. One 25 mm valve, each of four basic designs, was circulated to test centers which included four manufacturers and two FDA duplicators. The pressure drop and regurgitation data were then collected and summarized by the FDA. RESULTS: Considerable variation was observed in hydrodynamic performance measures of pressure drop across the valve and back flow leakage through the valve among the different duplicators. Despite the variations seen in these measures, the results from all centers showed that the valves conformed to certain minimum performance criteria. CONCLUSIONS: Despite the fact that the valves would have been judged to have met Minimum Performance Requirements of effective orifice area and regurgitant fraction, as specified in the international standard, variations in measurements existed among duplicators. Valve manufacturers should use a reference valve of similar design in hydrodynamic performance testing to assess the individual measurement conditions in the duplicator.

Comparison between experimental and computational methods for the acoustic and thermal characterization of therapeutic ultrasound fields.

For high intensity therapeutic ultrasound (HITU) devices, pre-clinical testing can include measurement of power, pressure/intensity and temperature distribution, acoustic and thermal simulations, and assessment of targeting accuracy and treatment monitoring. Relevant International Electrotechnical Commission documents recently have been published. However, technical challenges remain because of the often focused, large amplitude pressure fields encountered. Measurement and modeling issues include using hydrophones and radiation force balances at HITU power levels, validation of simulation models, and tissue-mimicking material (TMM) development for temperature measurements. To better understand these issues, a comparison study was undertaken between simulations and measurements of the HITU acoustic field distribution in water and TMM and temperature rise in TMM. For the specific conditions of this study, the following results were obtained. In water, the simulated values for p+ and p- were 3% lower and 10% higher, respectively, than those measured by hydrophone. In TMM, the simulated values for p+ and p- were 2% and 10% higher than those measured by hydrophone, respectively. The simulated spatial-peak temporal-average intensity values in water and TMM were greater than those obtained by hydrophone by 3%. Simulated and measured end-of-sonication temperatures agreed to within their respective uncertainties (coefficients of variation of approximately 20% and 10%, respectively).

Thermal safety simulations of transient temperature rise during acoustic radiation force-based ultrasound elastography.

Ultrasound transient elastography is a new diagnostic imaging technique that uses acoustic radiation force to produce motion in solid tissue via a high-intensity, long-duration "push" beam. In our previous work, we developed analytical models for calculating transient temperature rise, both in soft tissue and at a bone/soft tissue interface, during a single acoustic radiation force impulse (ARFI) imaging frame. The present study expands on these temperature rise calculations, providing applicable range assessment and error analysis for a single ARFI frame. Furthermore, a "virtual source" approach is described for temperature and thermal dose calculation under multiple ARFI frames. By use of this method, the effect of inter-frame cooling duration on temperature prediction is analyzed, and a thermal buildup phenomenon is revealed. Thermal safety assessment indicates that the thermal dose values, especially at the absorptive bone/soft tissue interface, could approach recommended dose thresholds if the cooling interval of multiple-frame ARFI elastography is too short.

Development and characterization of a tissue-mimicking material for high-intensity focused ultrasound.

A tissue-mimicking material (TMM) for the acoustic and thermal characterization of high-intensity focused ultrasound (HIFU) devices has been developed. The material is a high-temperature hydrogel matrix (gellan gum) combined with different sizes of aluminum oxide particles and other chemicals. The ultrasonic properties (attenuation coefficient, speed of sound, acoustical impedance, and the thermal conductivity and diffusivity) were characterized as a function of temperature from 20 to 70°C. The backscatter coefficient and nonlinearity parameter B/A were measured at room temperature. Importantly, the attenuation coefficient has essentially linear frequency dependence, as is the case for most mammalian tissues at 37°C. The mean value is 0.64f(0.95) dB·cm(-1) at 20°C, based on measurements from 2 to 8 MHz. Most of the other relevant physical parameters are also close to the reported values, although backscatter signals are low compared with typical human soft tissues. Repeatable and consistent temperature elevations of 40°C were produced under 20-s HIFU exposures in the TMM. This TMM is appropriate for developing standardized dosimetry techniques, validating numerical models, and determining the safety and efficacy of HIFU devices.

A comparison of the thermal-dose equation and the intensity-time product, Itm, for predicting tissue damage thresholds.

Thermal dose is the most generally accepted concept for estimating temperature-related tissue damage thresholds in high-intensity focused ultrasound (HIFU) procedures. However, another approach based on the intensity-time product I t(m) =D has been used, where D is a tissue-dependent damage threshold, I is the spatial-peak, temporal-average intensity and t is time. In this study, these two approaches were compared analytically by substituting a well-known soft-tissue solution for temperature vs. time into the thermal dose equation. From power law fits of I vs. t, m was found to fall between about 0.3 and 0.8. In terms of the intensity required for cell death for a given exposure time, the standard deviation of the error between the full thermal-dose formulation and the I t(m) =D prediction based upon the power-law fit was less than 5% for focal beam diameters up to 3 mm. Thus, for the practical range of HIFU parameters examined, the intensity-time product relationship is equivalent to the thermal dose formulation.

Egg white as a blood coagulation surrogate.

Egg white, a protein-containing solution, is characterized as a blood coagulation surrogate for the acoustical and thermal evaluation of therapeutic ultrasound, especially high intensity focused ultrasound (HIFU) devices. Physical properties, including coagulation temperature, frequency dependent attenuation, sound speed, viscosity, and thermal properties, were measured as a function of temperature (20-95 degrees C). Thermal coagulation and attenuation (5-12 and 1 MHz) of cow blood, pig blood, and human blood also were assessed and compared with egg white. For a 30 s thermal exposure, both egg white and blood samples (3 mm thickness) started to denature at 65 degrees C and coagulate into an elastic gel at 85 degrees C. The attenuation of egg white was found to be similar to that of the blood samples, having values of 0.23f(1.09), 1.58f(0.61), and 2.7f(0.5) dB/cm at 20, 75, and 95 degrees C, respectively. This significant attenuation increase with temperature was determined to be caused mainly by bubble cavity formation. The other temperature-dependent parameters are also similar to the reported values for blood. These properties make egg white a potentially useful bench testing tool for the safety and efficacy evaluation of therapeutic ultrasound devices.

A novel study of mechanical heart valve cavitation in a pressurized pulsatile duplicator.

Submission of data regarding the cavitation potential of a mechanical heart valve is recommended by the U.S. Food and Drug Administration in the device-review process. An acoustic method has long been proposed for cavitation detection. However, the question as to whether such a method can differentiate the cavitation noise from the mechanical closing sound has not been sufficiently addressed. In this study, cavitation near a Medtronic Hall tilting disc valve was investigated in a pressurized pulsatile duplicator. The purpose of pressurizing the testing chambers was to prevent cavitation under a normally cavitating loading condition to isolate the mechanical closing sound. By comparing the sound signals before and after pressurization, some noticeable differences were found between them. In the time domain, the intensity of the sound under a cavitating condition was much higher. In the frequency domain, the energy distribution of a sound signal was distinctively different depending on whether cavitation occurred or not. The valve closing sound had a large amount of energy in the low-frequency range (less than about 25 kHz). When cavitation took place, the sound energy shifted toward the high-frequency range (from 25 to 500 kHz).

Development and characterization of a blood mimicking fluid for high intensity focused ultrasound.

A blood mimicking fluid (BMF) has been developed for the acoustic and thermal characterizations of high intensity focused ultrasound (HIFU) ablation devices. The BMF is based on a degassed and de-ionized water solution dispersed with low density polyethylene microspheres, nylon particles, gellan gum, and glycerol. A broad range of physical parameters, including attenuation coefficient, speed of sound, viscosity, thermal conductivity, and diffusivity, were characterized as a function of temperature (20-70 degrees C). The nonlinear parameter B/A and backscatter coefficient were also measured at room temperature. Importantly, the attenuation coefficient is linearly proportional to the frequency (2-8 MHz) with a slope of about 0.2 dB cm(-1) MHz(-1) in the 20-70 degrees C range as in the case of human blood. Furthermore, sound speed and bloodlike backscattering indicate the usefulness of the BMF for ultrasound flow imaging and ultrasound-guided HIFU applications. Most of the other temperature-dependent physical parameters are also close to the reported values in human blood. These properties make it a unique HIFU research tool for developing standardized exposimetry techniques, validating numerical models, and determining the safety and efficacy of HIFU ablation devices.

The risk of exposure to diagnostic ultrasound in postnatal subjects: thermal effects.

This review evaluates the thermal mechanism for ultrasound-induced biological effects in postnatal subjects. The focus is the evaluation of damage versus temperature increase. A view of ultrasound-induced temperature increase is presented, based on thermodynamic Arrhenius analyses. The hyperthermia and other literature revealed data that allowed for an estimate of a temperature increase threshold of tissue damage for very short exposure times. This evaluation yielded an exposure time extension of the 1997 American Institute of Ultrasound in Medicine Conclusions Regarding Heat statement (American Institute of Ultrasound in Medicine, Laurel, MD) to 0.1 second for nonfetal tissue, where, at this exposure time, the temperature increase threshold of tissue damage was estimated to be about 18 degrees C. The output display standard was also evaluated for soft tissue and bone cases, and it was concluded that the current thermal indices could be improved to reduce the deviations and scatter of computed maximum temperature rises.

Acoustic power calibration of high-intensity focused ultrasound transducers using a radiation force technique.

To address the challenges associated with measuring the ultrasonic power from high-intensity focused ultrasound transducers via radiation force, a technique based on pulsed measurements was developed and analyzed. Two focused ultrasound transducers were characterized in terms of an effective duty factor, which was then used to calculate the power during the pulse at high applied power levels. Two absorbing target designs were used, and both gave comparable results and displayed no damage and minimal temperature rise if placed near the transducer and away from the focus. The method yielded reproducible results up to the maximum pulse power generated of approximately 230 W, thus allowing the radiated power to be calibrated in terms of the peak-to-peak voltage applied to the transducer.

On the closing sounds of a mechanical heart valve.

In the 1994 Replacement Heart Valve Guidance of the U.S. Food and Drug Administration (FDA), in-vitro testing is required to evaluate the potential for cavitation damage of a mechanical heart valve (MHV). To fulfill this requirement, the stroboscopic high-speed imaging method is commonly used to visualize cavitation bubbles at the instant of valve closure. The procedure is expensive; it is also limited because not every cavitation event is detected, thus leaving the possibility of missing the whole cavitation process. As an alternative, some researchers have suggested an acoustic cavitation-detection method, based on the observation that cavitation noise has a broadband spectrum. In practice, however, it is difficult to differentiate between cavitation noise and the valve closing sound, which may also contain high-frequency components. In the present study, the frequency characteristics of the closing sound in air of a Björk-Shiley Convexo-Concave (BSCC) valve are investigated. The occluder closing speed is used as a control parameter, which is measured via a laser sweeping technique. It is found that for the BSCC valve tested, the distribution of the sound energy over its frequency domain changes at different valve closing speeds, but the cut-off frequency remains unchanged at 123.32 +/- 6.12 kHz. The resonant frequencies of the occluder are also identified from the valve closing sound.

Effects of valve characteristics on the accuracy of the Bernoulli equation: a survey of data submitted to the U.S. FDA.

BACKGROUND AND AIM OF THE STUDY: In 1988, valve manufacturers petitioned the U. S. Food & Drug Administration (FDA) to replace catheter with Doppler ultrasound measurements of pressure gradient (delta P) in clinical studies. Manufactures agreed to submit bench data validating the Bernoulli equation used to calculate delta P = delta P = K(Vd2 - Vp2), where K = constant, Vd = distal Doppler velocity, and Vp = proximal Doppler velocity. Previous studies suggest that K may vary from the idealized 4.0, which could lead to incorrect valve assessment and clinical errors. METHODS: Variation in K-values in marketing application data submitted to the FDA was assessed. Pulse duplicator data included four bileaflet valves, two stented bioprostheses, and seven stentless bioprostheses, sized from 19 to 33 mm. Effects of valve type, valve size, blood-mimicking fluid used, and distal pressure tap position (DPTP) were evaluated via an analysis of variance. RESULTS: K-values varied from 2.50 to 7.40 (n = 90). K was found to be dependent on valve type (p < 0.0001), blood-mimicking fluid (p < 0.0001) and DPTP (p < 0.0001), but not valve size. At DPTP = 30 mm, K = 3.43 +/- 0.56, 5.15 +/- 0.81, and 4.81 +/- 1.02, for bileaflet, stented and stentless valves, respectively. K averaged 10% less using the 100-mm DPTP, due to pressure recovery. Variations due to blood-mimicking fluid were likely related to the fluid density. CONCLUSION: Variations due to DPTP and fluid used are consistent with physical mechanisms of pressure recovery and fluid density. Results from previous studies have suggested that effects of valve type on K are also real. The magnitude of these effects appeared to be +/- 25%. Extrapolation to patients is difficult, but clinicians should be aware that Doppler measurements may vary by similar amounts. Doppler pressure gradients should be interpreted qualitatively and moderated by other diagnostic measures of valve performance.

An analytic derivation for the transient temperature rise during an ultrasound pulse focused on bone.

An analytic derivation is given for the maximum transient temperature rise due to millisecond ultrasound (US) pulses focused on bone. The temperature rise is found to have, within a small correction factor, a square-root dependence on the pulse duration and is independent of the focal diameter. The equation developed is essentially the same as that found in a previous paper that obtained the formula by numerical methods and subsequent curve fitting.

Models and regulatory considerations for transient temperature rise during diagnostic ultrasound pulses.

A new diagnostic ultrasound (US) technique, sometimes called radiation force imaging, produces and detects motion in solid tissue or acoustic streaming in fluids via a high-intensity beam. Current models for estimating temperature rise during US exposure calculate the steady-state rise, using time-averaged acoustic output, as the worst case for safety consideration. Although valid for very short pulses, this analysis might not correspond to a worst-case scenario for the longer pulses or pulse bursts, up to hundreds of ms, used by this newer method. Models are presented to calculate the transient temperature rise from these pulse bursts for both the bone at focus and soft tissue situation. It is shown, based on accepted time-temperature dose criteria, that, for the bone at focus case and pulse lengths and intensities utilized by these methods, temperature may increase to levels that raise safety concerns. Also, regulatory aspects of this modality are analyzed in terms of the current FDA acoustic output limits for diagnostic US devices.

A theoretical assessment of a thermal technique to measure acoustic power radiated by ultrasound transducers.

The parameters affecting the temperature rise in an insonified absorber are studied computationally. Finite-element and analytical solutions are obtained for the transient energy equation in a cylindrical absorber. When the ultrasound beam radius is less than the radius of the absorber, the temperature field is seen to be considerably more complex than when the absorber cross section is uniformly heated. Circumstances in which power predictions based upon uniform heating would result in appreciable error are identified. The rise time required to achieve equilibrium is studied as a function of operational parameters, including absorber geometry and thermal properties as well as ultrasound beamwidth and frequency. The rise time is seen to increase approximately as the square of the absorber length, while optimized temperature rise increases linearly with absorber length, demonstrating a tradeoff in ultrasound power determination via equilibrium temperature measurements: longer lengths produce higher sensitivity, but also longer times before measurements can be made. A transient technique that may bypass this tradeoff is suggested.